DDX41_Rescue_CRISPR

DDX41 is frequently mutated in hereditary cases of acute myeloid leukaemia. Individuals commonly acquire a somatic mutation in the second DDX41 allele before progression, this is supposed to result in a significant reduction in the function of the protein. Interestingly studies in murine models have shown that biallelic loss of DDX41 is detrimental in highly proliferating cells, therefore it remains to be understood how leukaemia cells overcome this proliferative disadvantage. CRISPR-Cas9 drop-out screens have found that DDX41 loss was lethal in 32D cells. For the purpose of this study, 32D cas9 cells were transduced with a single guide genome wide CRISPR library and then with a gRNA against DDX41, we are hoping to identify cooperating mutations that rescue the lethal phenotype in 32D cells and could give insight into mechanisms of transformation.